The Gene: An Intimate History - Siddhartha Mukherjee Page 0,80

as a case in point. Walter Noel had inherited two abnormal copies of the hemoglobin B gene. Every cell in his body carried the two abnormal copies (every cell in the body inherits the same genome). But only red blood cells were affected by the altered genes—not Noel’s neurons or kidneys or liver cells or muscle cells. What enabled the selective “action” of hemoglobin in red blood cells? Why was there no hemoglobin in his eye or his skin—even though eye cells and skin cells and, indeed, every cell in the human body possessed identical copies of the same gene? How, as Thomas Morgan had put it, did “the properties implicit in genes become explicit in [different] cells?”

In 1940, an experiment on the simplest of organisms—a microscopic, capsule-shaped, gut-dwelling bacterium named Escherichia coli—provided the first crucial clue to this question. E. coli can survive by feeding on two very different kinds of sugars—glucose and lactose. Grown on either sugar alone, the bacterium begins to divide rapidly, doubling in number every twenty minutes or so. The curve of growth can be plotted as an exponential line—1, 2-, 4-, 8-, 16-fold growth—until the culture turns turbid, and the sugar source has been exhausted.

The relentless ogive of growth fascinated Jacques Monod, the French biologist. Monod had returned to Paris in 1937, having spent a year studying flies with Thomas Morgan at Caltech. Monod’s visit to California had not been particularly fruitful—he had spent most of his time playing Bach with the local orchestra and learning Dixie and jazz—but Paris was utterly depressing, a city under siege. By the summer of 1940, Belgium and Poland had fallen to the Germans. In June 1940, France, having suffered devastating losses in battle, signed an armistice that allowed the German army to occupy much of Northern and Western France.

Paris was declared an “open city”—spared from bombs and ruin, but fully accessible to Nazi troops. The children were evacuated, the museums emptied of paintings, the storefronts shuttered. “Paris will always be Paris,” Maurice Chevalier sang, if pleadingly, in 1939—but the City of Lights was rarely illuminated. The streets were ghostly. The cafés were empty. At night, regular blackouts plunged it into an infernally bleak darkness.

In the fall of 1940, with red-and-black flags bearing swastikas hoisted on all government buildings, and German troops announcing nightly curfews on loudspeakers along the Champs-Élysées, Monod was working on E. coli in an overheated, underlit attic of the Sorbonne (he would secretly join the French resistance that year, although many of his colleagues would never know his political proclivities). That winter, with his lab now nearly frozen by the chill—he had to wait penitently until noon, listening to Nazi propaganda on the streets while waiting for some of the acetic acid to thaw—Monod repeated the bacterial growth experiment, but with a strategic twist. This time, he added both glucose and lactose—two different sugars—to the culture.

If sugar was sugar was sugar—if the metabolism of lactose was no different from that of glucose—then one might have expected bacteria fed on the glucose/lactose mix to exhibit the same smooth arc of growth. But Monod stumbled on a kink in his results—literally so. The bacteria grew exponentially at first, as expected, but then paused for a while before resuming growth again. When Monod investigated this pause, he discovered an unusual phenomenon. Rather than consuming both sugars equally, the E. coli cells had selectively consumed glucose first. Then the bacterial cells had stopped growing, as if reconsidering their diet, switched to lactose, and resumed growth again. Monod called this diauxie—“double growth.”

That bend in the growth curve, small though it was, perplexed Monod. It bothered him, like a sand grain in the eye of his scientific instinct. Bacteria feeding on sugars should grow in smooth arcs. Why should a switch in sugar consumption cause a pause in growth? How might a bacterium even “know,” or sense, that the sugar source had been switched? And why was one sugar consumed first, and only then the second, like a two-course bistro lunch?

By the late 1940s, Monod had discovered that the kink was the result of a metabolic readjustment. When bacteria switched from glucose to lactose consumption, they induced specific lactose-digesting enzymes. When they switched back to glucose, these enzymes disappeared and glucose-digesting enzymes reappeared. The induction of these enzymes during the switch—like changing cutlery between dinner courses (remove the fish knife; set the dessert fork)—took a few minutes, thereby resulting in the observed pause in growth.

To Monod, diauxie suggested that genes